This invention relates to antibodies specific for cretinekinase-MB antibodies and a process for the production thereof.
The determination of the activity of creatinekinase (ATP: creatine-phosphotransferase, E.C. 2.7.3.2; abbreviation: CK) in serum is considered the most sensitive laboratory method for diagnosing diseases of skeletal muscles and the myocardium, especially in the case of myocardial infarction. However, differentiation between trauma of skeletal muscles and the myocardium is difficult, especially in making a differential diagnosis of myocardial infarction. Reliable differentiation is impossible by a determination of the total CK activity. Therefore, attempts have been made to increase the reliability of the evidence provided by measurement of CK activity in differential diagnosis by measuring the activity of other enzymes in the serum and correlating the resulting measurements with each other, for example, by forming the quotient CK/glutamic oxalacetic transaminase. However, quotients of this type cannot be used to differentiate between cardiac infarction and pulmonary infarction or between cardiac infarction and secondary shock resulting from other causes.
CK occurs in the body in the form of three isoenzymes, namely CK-MM, for example, in muscles; CK-BB, for example, in the brain; and as a hybrid CK-MB, consisting of an M and a B subunit, for example, in the myocardium. The CK activity occurring in the blood serum is normally due to the CK-MM isoenzyme, because CK-BB does not pass through the fluid/blood barrier and CK-MB is restricted to certain organs, for example, the myocardium. However, in case of damage to the myocardium as in the case of cardiac infarction, CK-MB is released into the blood serum and can be detected therein.
Quantitative determination of this isoenzyme along with CK-MM in the serum is considered the most sensitive laboratory method and is of the greatest value in differential diagnosis of cardiac infarction. Although a few other organs, in addition to the myocardium, contain CK-MB, e.g., the pancreas, the diaphragm, the aorta, the lungs, and the uterus, the activity of these organs is less by a factor of 100 than in the myocardium, so that any CK-MB activity liberated from the aforementioned organs is below the limits of detection.
Heretofore, activity determinations of CK-MB were based primarily on electrophoretic and chromatrographic methods, or on immunological determinations with antibodies to cause precipitation. All of these methods had the feature in common that they were unsuitable for a rapid diagnostic determination of CK-MB activity.
This invention is based on the development of antibodies, with which it is possible to conduct a quantitative determination of CK-MB activity, especially a rapid determination of activity of this isoenzyme in body fluids.
This problem is solved, in accordance with the invention, by the production of heretofore unknown highly specific antibodies against the subunit M of CK-MM and CK-MB.